The renal function was assessed in 51 bipolar patients on multiple-dosage lithium maintenance therapy from 1 to 22 years, after placing them on single (HS) dosage for 12–18 months. Serum lithium levels were maintained constant at a level of 0.8 mg/1. The patients were divided into three groups according to duration of previous multiple doses (b.i.d.–q.i.d.) Li therapy; less than 5 years; 5–10 years; 10–22 years. The improvement in water handling occurred only in the previously shortest multiple-dosage-treated patients and the duration of previous multiple dosage negatively influenced water handling; however, all laboratory analyses remained within normal limits. None of the patients showed clinical worsening or had an affective episode. The separate analyses showed associated gender differences in urinary volume, serum creatinine, and creatinine clearance values. Our findings confirmed the beneficial renal reaction to single-dose posology, as well the female sensitivity to Li therapy in general, and especially with concomitant antipsychotic med