Rats were treated once with doses of haloperidol or of droperidol below and above the acute ID50 vs the dopamine agonist apomorphine; they were later challenged with an acute dose of apomorphine (0.3 mg/kg, SC) and rated for stereotyped behavioral responses. The two neuroleptics were similar in acute anti-apomorphine potency (ID50 = 0.12 and 0.18 mg/kg for haloperidol and droperidol, respectively). The antidopaminergic effects of droperidol persisted for nearly 1 week and those of haloperidol lasted for 20-40 days, depending on the dose given. The computed half-time of disappearance of their antidopaminergic effects was 7.6 +/- 1.0 days and 0.59 +/- 0.17 days for haloperidol and droperidol, respectively, following a dose of 0.3 mg/kg, and these indices of duration of action did not vary significantly at doses between 0.1 and 1.0 mg/kg. Haloperidol reduced the acute entry of 3H-apomorphine into brain by 21.5% 1 week later. Treatment with apomorphine alone just prior to haloperidol (both at 0.3 mg/kg) prevented the prolonged antidopaminergic effects of the neuroleptic evaluated 1 week later. These results indicate that some neuroleptics may have very prolonged activity or retention in tissue at sites of action, even after moderate, single doses. Caution is recommended in the interpretation of studies which assume "neuroleptic-free" conditions of subjects previously exposed to a neuroleptic agent.