Evidence supporting the use of lithium in the long-term care of bipolar disorder patients is unequaled; fluctuations of lithium (Li) plasma concentration, however, are associated with side effects at peak, and symptomatic states at trough, Li plasma levels. Slow release preparations represent a means of maintaining stable Li plasma levels and thereby: [1] reducing side effects, [2] requiring fewer daily administrations, [3] possibly providing more stable therapeutic response and [4] improving patient compliance. The aim of the present study is to investigate the long-term efficacy and tolerability of a new prolonged release formulation of Li, called Carbolithium Once A Day (OAD), in patient with bipolar disorder previously treated with standard Li. Upon completion, the study will last for 2 years; this paper, however, is an interim analysis of tolerability and clinical outcome of 4-month (N = 27) and 6-month (N = 15) completers. Li plasma levels and doses remained relatively stable throughout the periods of observation (days 30, 60, 120, and 180). Doses of OAD did not differ significantly from doses on prior standard Li in subjects at 4 months (681 +/- 160 and 665 +/- 154 mg/d, respectively) or 6 months (647 +/- 161 and 710 +/- 192 mg/d, respectively). Correspondingly, Li plasma levels on previous traditional Li and on OAD were not significantly different at 4-months (0.47 vs 0.46 mEq/l respectively. Wilcoxon z = 0.456, p = 0.648) or 6-months (0.47 and 0.51 mEq/l respectively, Wilcoxon z = 0.220, p = 0.826). Among 4-month completers, improvement in mania scores was significant (Wilcoxon z = 2.366, p = 0.018), but was not at 6-months. Significant reduction of scores on the Melancholia Scale was observed among both the 4 and 6-month completers (Wilcoxon z = 3.516, p < 0.001 and z = 2.521, p = 0.012, respectively). The occurrence of side effects was significantly reduced among patients switched from traditional Li. All patients declared their preference for OAD over traditional Li for its better tolerability and case of use at day 30.