Drug companies would need to explore alternative study designs to evaluate the effects of the new neuroleptics in neuroleptic-responsive patients. One approach, which may or may not obtain approval of the institutional review board, would be to discontinue medication for neuroleptic-responsive patients, wait for patients to relapse, and then randomly assign them to treatment. This would probably require the drug company to pay for a period of hospitalization, and patients would probably need a financial incentive to participate. An alternative, somewhat less expensive, approach would be to identify neuroleptic-responsive patients on a regimen of standard neuroleptics and to randomly assign them to stay on the regimen, to switch to an atypical antipsychotic, or to take placebo. Patients would then have to be carefully monitored for a prolonged period of time (e.g., 6 months). This could be done primarily with outpatients, although hospitalization would be required for some patients.Until studies involving neuroleptic-responsive patients with schizophrenia are conducted, one cannot say with certainty whether the new atypical neuroleptics will be as effective as the old agents for positive symptoms in neuroleptic-responsive patients.