Although second-generation antipsychotics have notabLe benefits as compared to typical antipsychotics, their use has been associated with metaboLic disturbances, such as alterations of glucose homeostasis. It is still being debated whether this is a class effect of second-generation antipsychotics. We conducted a prospective, open study comparing body weight, parameters of insuLin resistance in schizophrenia patients treated with either clozapine ( n = 10) or amisuLpride ( n = 12). All parameters were assessed monthly over a period of 12 to 16 weeks. Body mass index (BMI), fasting serum insulin Levels and the Homeostasis Model Assessment (HOMA) index for insulin resistance increased significantly in patients treated with clozapine. None of these parameters increased significantly in patients treated with amisulpride. This study indicates that treatment with clozapine appears to have a higher risk to Lead to metabolic disturbances than amisupride.