Replacement of calcium in artificial sea water (ASW) by nickel causes a loss of calcium at a single exponential rate (tau = 23.2 min) and the loss of contracture response to acetylcholine (ACh) in the anterior byssus retractor muscle of Mytilus edulis L. The ACh contracture response is lost at two rates; 93% of the ACh contracture response is lost rapidly (tau = 7.43 min) and the remaining 7% of ACh contracture response is lost slowly (tau = 66.6 min). The rapid phase of loss of ACh contracture corresponds to the rapid exponential uptake of nickel (tau = 6.5 min). The loss of ACh contracture response is attributed to the displacement of calcium from membrane release sites by nickel. In O-Ca-Mg ASW, the ACh contracture responses are well maintained over a 35-min period when stimulated by ACh every 5 min. Stimulation by ACh after 1, 20 and 40 min in O-Ca-Mg ASW results in a reduction of ACh contracture response to 15% of the response in Ca ASW. Similar treatment in O-Ca-Ni ASW reduces the ACh contracture response to 4%. Potassium and caffeine contracture responses at 1, 20 and 40 min in O-Ca-Mg ASW are reduced to 25 and 28%. Similar treatment in O-Ca-Ni ASW produces a block of potassium contracture response and reduces caffeine contracture response to 3%. Our 45Ca uptake data demonstrate that calcium influx is not required for the ACh contracture responses of anterior byssus retractor muscle.