An outbreak of unusual reactions was observed among epileptic patients as Monson State School in Palmer, Massachusetts. Patients in about half of the buildings in the school were receiving isoniazid and the others, a matching placebo. Neither the patients nor the staff knew which product had been randomly assigned to a building. Soon after the start of the trial some patients unexpectedly developed signs and symptoms of excessive sedation or incoordination which disappeared when their tuberculosis prophylactic medication was stopped. Isoniazid appeared to be associated with the reactions. Of 845 patients taking placebo 23 had reactions (2.7%), compared with 70 patients with reactions among 637 taking isoniazid (11.0%). In reinstituting treatment in 55 patients who had received isoniazid, 46 had a recurrence of symptoms compared with only 2 of 19 patients who had received placebo. Reactions were observed more frequently among females than males, and appeared to be related to age among females. No relation was observed with serum concentrations of isoniazid. All patients with reactions were also receiving both phenobarbital and diphenylhydantoin as anticonvulsant medication, as were most residents in the school. The nature of the reaction and reported observations in animals suggest that isoniazid may potentiate the action of these drugs.