Fourteen patients with a history of mania satisfying DSM-III criteria were entered into a randomised double-blind placebo-controlled crossover trial, spending four weeks on each of lithium and placebo. All patients had been well and stable on lithium for at least 18 months and were not taking any other psychotropic drugs. Seven patients (50%) had a relapse of their manic illness and a further two had to be withdrawn because they recognised signs of incipient relapse. One of these became overtly manic after restarting lithium. The seven definite and the two possible relapses occurred in the placebo phase; this finding was unlikely to have arisen by chance. The relapses started 13-19 days after placebo substitution. These results have important implications in the management of lithium prophylaxis by all doctors, particularly those who, for any reason, are considering withdrawal of lithium from their patients.