Background: It has been known for over a century that abnormalities of glucose metabolism are more common in those suffering from certain forms of mental illness, but only in the past few years has there been any attempt to establish the nature of the association. Most evidence suggesting an association between schizophrenia, antipsychotics and diabetes has been based on retrospective studies not controlled for important confounders. Objectives: To study the association between the use of antipsychotic agents and hyperglycaemia, the association between hyperglycaemia and the class or type of antipsychotic agent, as well as the relationship between the use of antipsychotic agents and weight gain among patients with schizophrenia. Method: A total of 418 subjects made up of 209 cases and 209 controls took part in the study. Fasting blood sugar, weight and height were measured at the beginning of the study and repeated 4 months thereafter. The 209 cases all had a diagnosis of schizophrenia, and took antipsychotic agents after the initial estimation of their fasting blood sugar level. The controls (comparison group) consisted of 209 first degree relatives who had no history of schizophrenia and took no antipsychotics. Results: There was an 85.8% response rate among those approached for inclusion into the study. There were more males (53.6%) than females (46.4%). The mean initial fasting blood sugar among the cases was 4.24mmol/l (SD=0.36), with a mean final fasting blood sugar of 5.26mmol/l (SD=0.67) (t=22.13, df=208, p<0.001) at the end of the study. Among the controls, the mean initial fasting blood sugar was 4.23mmol/l (SD=0.42), and the mean final fasting blood sugar was 4.22mmol/l (SD=0.41) (t=0.86,df=208, p=0.38) at the end of the study. There was a significant association between antipsychotic use and hyperglycaemia (x2=27.72, df =1, p<0.001). The prevalence of hyperglycaemia was 12.4%. Mean weight gain for cases was 4.06kg (SD=3.05), while for the controls the mean weight gain was 0.06kg (SD=0.51). The use of antipsychotics (both typical and atypical) was associated with significant weight gain (t=18.65, df= 416, p<0.001). Conclusion: The use of antipsychotic agents led to increased hyperglycaemia and weight gain. This is in keeping with previous reports.