Elevation of serum creatine kinase (CK) concentrations occurs almost invariably in neuroleptic malignant syndrome (NMS). However, the role of CK levels in the diagnosis of the syndrome remains controversial. This study measured CK levels in patients who became pyrexial while on psychotropic medication and thereby mimicked some of the features of NMS. In all of these cases a diagnosis of infectious illness was made and patients responded to appropriate antibiotic therapy without alteration in psychotropic medication. Two other groups were studied for comparison – patients on psychotropics who were apyrexial and patients who became pyrexial but were not on psychotropics. Significant, unexpected elevations of CK were documented in 70% of those patients who became pyrexial while on psychotropics – in three cases elevation of concentrations to more than 1000 IU/1 (ten times reference value) were found. Thirty per cent of patients who became pyrexial but were not on psychotropics also developed elevation of CK but this was of a much smaller magnitude (lt; 200 IU/1 in five out of six cases). The results of the study suggest that elevation of CK is a non-specific finding, particularly in patients who become pyrexial on psychotropics. Use of CK as a diagnostic criterion may lead to overdiagnosis of NMS.