Following a malfunction on the TARDIS console and the bleating of a klaxon indicating something is amiss, the Doctor insists the fault locator shows nothing is wrong and it is safe to venture outside. He leads his companions Ian, Barbara and Susan to the world beyond and within minutes they find a dead giant earthworm followed by a large deceased ant. They seem to have died immediately. After some deduction the travellers realise they have arrived on Earth but have shrunk in size to mere inches.
Ian is investigating a discarded matchbox when someone picks it up and he is hurled around inside. That someone is a government scientist called Farrow. He is visited at his home by a callous industrialist named Forester to tell him that his application for DN6, a new insecticide, has been rejected. In reality DN6 should not be licensed: it is far too deadly to all insect life. When they fall out over this news, Forester shoots Farrow and leaves him for dead on the lawn.
The Doctor, Barbara and Susan hear the gunshot as an enormous explosion, and head for the house. They find Ian unhurt near the dead body and surmise a murder has taken place but can do little about it. They are determined, however, to ensure the murderer is brought to justice despite their microscopic size. While avoiding a cat, the travellers get split up again with Ian and Barbara hiding in a briefcase. The giant Forester returns to the lawn and collects the briefcase, taking it inside to the laboratory. His aide, Smithers, arrives and suspects him of murder, but does not report him for fear of undermining the DN6 project to which he has given his life.
The Doctor and Susan scale a drain pipe to gain access to the house and locate their friends, braving the height as they go. Meanwhile Ian and Barbara examine the laboratory and encounter a giant fly, which is killed instantly when it contacts sample seeds that had been sprayed with DN6. Barbara foolishly touched one seed earlier and soon starts to feel unwell. Nevertheless, attracted by Susan’s voice in the reverberating plug hole, the four friends are reunited.
Forester has meanwhile doctored Farrow’s report so as to give DN6 the licence he wants and, disguising his voice as Farrow’s, makes a supportive phonecall to the ministry to the same effect. This is overheard by the local telephone operator, Hilda Rowse, and her policeman husband, Bert, who start to suspect something is wrong.
The Doctor has meanwhile realised the deadly and everlasting nature of DN6 and the probable contamination of Barbara. They try to alert someone by hoisting up the phone receiver with corks, but cannot make themselves heard. Hilda notes the engaged signal, however, and she and Bert become even more concerned. Forester and Smithers return to the lab and correct the engaged handset and then Hilda rings to check things are okay. She rings again moments later and asks for Farrow and, when Forester impersonates him, immediately spots the faked voice and so knows there is something badly wrong. Bert heads off to the house to investigate.
The Doctor and his companions decide to start a fire to attract attention to the house and succeed in setting up an aerosol can of insecticide and a lab bench gas jet as a bomb. This coincides with Smithers discovering the true virulence of DN6 - it's lethal to everything - and demanding Forester stop seeking a licence. Forester spots the makeshift bomb, which goes off in his face. Smithers retrieves the gun as PC Rowse arrives and then places both under arrest.
Their work done, the travellers return to the TARDIS and the Doctor reconfigures the machine to return them to normal size. Barbara, who was on the verge of death, recovers on being returned to full size; the insecticide and seed responsible aboard the TARDIS shrinking to their real microscopic and minuscule sizes.