The adenylate cyclase of bloodstream forms of Trypanosoma brucei is regulated by Ca2+. 2. The Ca2+-stimulated activity is not inhibited by trifluperazine, tentatively suggesting that the stimulation may not be mediated by calmodulin. 3. The Ca2+-binding site of the receptor regulating the adenylate cyclase is buried within the hydrophobic region of the plasma membrane and is not exposed to either the inner or the outer aqueous-phase bounding the membrane in unstimulated cells. 4. The response of the adenylate cyclase to stimulation by Ca2+ within the membrane is a transient increase in activity followed by a period of 'down regulation'. 5. The 'down regulation' of the adenylate cyclase also occurs by a Ca2+-dependent mechanism.