A recent survey of clinicians' opinions suggested that antipsychotic polypharmacy is reserved for particularly severe cases, and that it is intended to avoid high doses of a single drug. In the present study, we tested these clinicians' reasons for antipsychotic polypharmacy in a sample of Italian psychiatric inpatients. During a 6-year recruitment period, all psychiatric patients receiving antipsychotic therapy at discharge from an inpatient facility were included. Sociodemographic and clinical data were collected, and the 18-item version of the Brief Psychiatric Rating Scale was administered on admission and before discharge. At discharge, data on length of inpatient stay, psychotropic drug therapy and treatment adherence were collected. Prescribed daily doses were converted into multiples of the defined daily doses. A total of 354 inpatients receiving antipsychotic treatment at discharge were included. Of these, 100 (28%) were discharged with two or more antipsychotic drugs. After background group differences were controlled for, positive symptoms, manic/hostility symptoms and polypharmacy on admission were predictors of polypharmacy at discharge. The risk of high-dose antipsychotics in patients receiving polypharmacy at discharge was 10-fold higher than that in patients receiving one antipsychotic (odds ratio 10.70, 95% confidence interval 4.78-23.97, P<0.001). The perception of clinicians is to reserve antipsychotic polypharmacy for severe, persistent and difficult-to-treat cases, and this was confirmed by the finding that patients discharged on two or more antipsychotic agents were more severely ill on admission. Conversely, the theoretical advantage of avoiding a high dose of a single drug is counterbalanced by the documented disadvantage of administering high total doses.