The adenylate cyclase of Trypanosoma brucei is activated by local anaesthetics. 2. Activation of adenylate cyclase by the local anaesthetic, benzyl alcohol, requires Ca2+. 3. The kinetics of the presteady state reveal that the activation step occurs prior to and is separate from the catalytic step. 4. The activation step in the presence of Ca2+ can be stimulated some 200-fold and is highly co-operative with respect to benzyl alcohol concentration. 5. The mechanism by which local anaesthetics activate may be by exposing the Ca2+ -binding site of the Ca2+ receptor which is oriented towards the hydrophobic regions of the plasma membrane in the basal state.