Schizophrenia is characterized by early onset and chronic lapse in most of the patients. The suffering associated with schizophrenia is enormous – for patients, families, and in society at large. Pharmacotherapy is the mainstay of treatment, without which most psychosocial treatment would not be possible. However, substantial variety in efficacy as well as frequently reported side effects are problems often encountered with current antipsychotic treatment. Cytochrome P450 (CYP) enzymes are involved in the metabolism of most psychotropic drugs and characterized as the most important factor for individual variation to drug response. This study investigated pharmacotherapy of schizophrenic inpatients in seven different nursing homes receiving long-term antipsychotic treatment. Impact of environmental- and genetic factors on serum concentration of antipsychotics was studied. CYP-genotyping of isoenzymes CYP2C9, CYP2C19 and CYP2D6 were performed for both a patient group (n=109) and a control group (n=136). Clinical data were collected from records and medicine cards. Serum concentrations (trough) were obtained for all antipsychotics used by the patients. The patients were on average treated with 1.5 antipsychotics and 2.7 concomitant drugs. Our patient group received a total of 2.2 defined daily doses (DDD) of antipsychotics compared to an average of 1.2 DDD reported in a study of psychiatric hospital inpatients. The measured genotypes were not significantly different between the patient- and control group. Only one of the patients had been genotyped prior to the project. Patients being poor metabolizers had higher serum concentrations and patients being ultra rapid metabolizers had decreased serum concentrations from a given dose. CYP2D6 intermediate-metabolizer genotype appeared to be important in some patients, especially when other factors (e.g. environmental, polypharmacy) were present. Low doses of CYP2D6 inhibitors appeared to be of minor importance as long as it was the only factor influencing CYP activity. Use of CYP inducers led to decreased serum concentrations. Smoking did significantly decrease serum concentrations of CYP1A2 substrates and the induction seemed to be similar in heavy compared to light smokers. Pharmacotherapy in patients suffering from chronic schizophrenia is characterized by polypharmacy and somewhat high doses of antipsychotics. Both genetic and environmental factors appear to influence the serum concentration. CYP-genotyping combined with therapeutic drug monitoring can be an important tool in individualization of drug regimes. Reassessing the pharmacotherapy of some of these patients might lead to an improvement of their current treatment.