The present work was aimed at assessing the GTP-binding (Galphas subunit) protein expression in lithium-treated bipolar patients (BP). Mononuclear leukocyte Galphas protein and mRNA were measured both in patients and in a comparison group. The patient group consisted of 15 lithium-treated patients with bipolar affective disorder, all diagnosed as euthymic bipolars, and a comparison group of 15 drug-free healthy subjects. The method of competitive Reverse Transcriptase coupled to Polymerase Chain Reaction (RT-PCR) was used to estimate the relative abundance of Galphas mRNA, whereas the Western-immunoblot method was used to estimate Galphas levels. Results of both Galphas proteins and Galphas mRNA levels from patients were compared to those of non-treated control subjects. By using the competitive RT-PCR method, the Galphas mRNA displayed a significant decrease in the lithium-treated bipolar patients compared to non-treated controls: the ratio / was 1\81+/-0\05 versus 2\51+/-0\6 for BP and controls, respectively (Mann-Whitney test, < 0%sol;001). Studying the same groups with respect to their protein levels, it was shown that Galphas levels were also significantly decreased in the group of bipolar patients (normalized values to a standard yielded 81\2+/-21 per cent versus 122\5+/-25 per cent for BP and controls, respectively; Mann-Whitney test, < 0\001). Data indicated that lithium induces a decrease both in Galphas protein levels and in Galphas mRNA synthesis in BP with respect to drug-free healthy subjects. Copyright 2000 John Wiley & Sons, Ltd.