Several processes relating to the cholinergic system that are present in human blood were measured in samples obtained from patients with bipolar affective disorder, both before and during treatment with lithium, and from controls. The biochemical measurements include RBC and plasma choline concentrations, the kinetics of RBC choline uptake, plasma non-specific cholinesterase and RBC and plasma acetylcholinesterase. The RBC choline level is increased and the Vmax of the RBC choline uptake system is decreased in samples from lithium-free bipolar patients during manic episodes. There are no differences from control in the plasma choline levels or in the acetylcholinesterase enzyme activities in blood samples from the lithium-free or lithium-treated patients. Plasma non-specific cholinesterase is below control levels in all patients. Lithium treatment increases the RBC choline concentration to more than ten-times control levels and reduces the Vmax and the affinity for choline of the RBC choline transport system. In vitro addition of lithium does not replicate the effects of in vivo administration of lithium. Possible mechanisms for these effects of lithium are discussed. © 1986.