Cyclosporine (CsA) is frequently used for nontransplant indications such as autoimmune diseases. Unfortunately, side effects such as renal dysfunction and hypertension are frequently described in spite of close monitoring with CsA trough levels. The purpose of the present prospective cohort study was to use the CsA level obtained 6 h after the morning dose (T6) for CsA dose adjustment and its impact on observed side effects in 11 patients (44+/-17 years) treated with CsA for autoimmune diseases. Patients were monitored for CsA-related side effects at each outpatient visit, including blood pressure measurement, CsA trough and T6 levels and routine laboratory tests. Changes in blood pressure and biochemical parameters were compared to the previous visit (n = 244) and a change >30% was considered significant. Significant changes in monitored variables were observed in the following percentage of visits: increases in systolic/diastolic blood pressure (1.2), serum creatinine (6.1), potassium (0.8), and uric acid (6.3), and a decrease in magnesium (0.5). At the end of follow-up (20+/-12.5 months), CsA dose was reduced from 4.8+/-1.1 to 3.5+/-1 mg/kg/day (p = 0.004); serum creatinine, potassium, uric acid, hemoglobin, total cholesterol, effective renal plasma flow and glomerular filtration rate did not differ from baseline. Alkaline phosphatase increased from 63+/-19 to 82+/-21 U/l(p = 0.04) and magnesium decreased from 0.85+/-0.1 to 0.75+/-0.1 mmol/l (p = 0.02). Transient hypertension and reversible renal dysfunction was seen in 2 patients, respectively. In conclusion, CsA monitoring according to T6 levels may allow a lower CsA dose than the one usually recommended and reduce the incidence of side effects in patients with autoimmune diseases.