BACKGROUND: Clozapine is a uniquely effective antipsychotic, although its use is limited by the risk of neutropenia. Lithium is occasionally prescribed during a clozapine rechallenge, with the hope that it will prevent a second neutropenia or agranulocytosis. There are concerns, however, that lithium use will mask the onset of a neutropenia, leading to a more severe dyscrasia. The objective of this analysis was to determine the utility and safety of lithium coprescription in clozapine rechallenge. METHOD: A retrospective case analysis was performed of all patients who had experienced a previous clozapine-induced blood dyscrasia and had a clozapine rechallenge with lithium coprescribed in a tertiary referral center between September 1998 and September 2003. RESULTS: Twenty-five patients met the study criteria; 1 patient (4%) had a second episode of neutropenia or agranulocytosis while undergoing the rechallenge. This rate was significantly lower (p = .021) than the national (U.K.) rate (21.2%). Although recurrent dyscrasias were not more common, or more severe, than those seen with rechallenge in general, our single case did show some evidence that the patient's neutropenia was masked by lithium use. CONCLUSION: This study provides support for the utility of lithium in preventing neutropenias in rechallenge; extra vigilance may be required, however, to detect masked blood dyscrasias.