The authors' aim was to evaluate the safety and efficacy of a loading-dose regimen for initiating use of a depot medication, haloperidol decanoate, with patients who bad been maintained on oral haloperidol. Patients were given a loading dose of about 20 times their oral maintenance dose in divided injections during the first two weeks of conversion to depot medication. The dose of haloperidol decanoate was gradually reduced, dropping to about ten times the oral dose in the third and fourth months. No supplemental oral medication was used. Methods: Haloperidol decanoate was initiated using the loading-dose regimen in 16 chronically ill patients. Linver initial doses of haloperidol decanoate were used in two other groups of patients, one that received supplemental oral haloperidol and one that did not. Plasma levels of haloperidol, severity of illness, and side effects were monitored from baseline to 56 days after the beginning of depot therapy. Results: Patients who received the loading-dose regimen showed statistically significant clinical improvement and reduced side effects over baseline by the 28th day. The second group of patients also maintained therapeutic response but improved no further. The third group relapsed during the first month and were returned to a regimen of oral haloperidol by the second month. Conclusions: A loading-dose regimen for initiating treatment with haloperidol decanoate is safe and effective and can be useful in a clinical setting.