The circadian dynamics of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were simulated in Paramecium multimicronucleatum. The mathematical functions determined closely mimic the Ca2+ dependence of adenylate cyclase (AC) and guanylate cyclase (GC) activities as documented in P. tetraurelia. Patterns of cAMP concentration ([cAMP]), cGMP concentration ([cGMP ]), and the ratio [cGMP]/[cAMP] were calculated with respect to Ca2+ concentrations ([Ca2+]) fluctuating sinusoidally with a period of 24 hours at three different levels: low, medium, and high. The functions displayed varying patterns of [cAMP] characteristic for [Ca2+] fluctuating at each level, while patterns of [cGMP] and [cGMP]/[cAMP] almost paralleled [Ca2+] fluctuations. Similar patterns were observed for actual [cAMP] and [cGMP] measured during the light/dark cycle in P. multimicronucleatum, grown in axenic media additionally containing [Ca2+] at 25 (low), 100 (medium), or 400 (high) microM, respectively. The coincidence between simulated and measured fluctuations of [cAMP] and [cGMP] suggests that the circadian fluctuations of intracellular [Ca2+] primarily stimulate activities of AC and GC via their different degrees of Ca2+ dependence, which are ultimately responsible for the circadian spatiotemporal organization of various physiological functions in Paramecium.