To explore possible roles of calmodulin in Ca2+-induced ciliary reversal, we tested the effects of calmodulin antagonists on Triton-extracted models of Puru- mecium. In the extracted models prepared by the method of Naitoh and Kaneko [Science 176:523-524, 19721, the Ca2+-induced ciliary reversal was not inhibited by calmodulin antagonists, trifluoperazine (TFP), or 5-chloro-1 -naphthalenes& phone amide (W-7). However, in the presence of adenosine 3',5'-cyclic monophosphate (CAMP), whose concentration is below the one that alters the ciliary direction, TFP inhibited ciliary reversal and the models swam forward at lo-' M Ca2'. When the washing medium in the preparation of the extracted models was replaced with one containing MgC12, the extracted model showed sensitivity to calmodulin antagonists without addition of CAMP; at lo-' M Ca2+, 40 pM TFP or 100 p M W-7 inhibited the ciliary reversal and the models swam forward. Such effect of antagonists was abolished by an inhibitor of CAMP-dependent protein kinase. On the other hand, addition of CAMP enhanced the inhibitory effect of antagonists. These results suggest that calmodulin antagonists act to increase the extent of CAMP-dependent protein phosphorylation that inhibits the Ca2'-induced ciliary reversal.