We measured the levels of calmodulin in brain tissue as well as in other tissues by a specific radioimmunoassay. Fisher-344 rats with ages of 3, 13, 23, and 29 months were used. IR-calmodulin levels were reduced in the cortex, striatum, and anterior pituitary but not in the hypothalamus (although there was a tendency for reduction in the latter tissue). No significant decreases in IR-calmodulin were observed in gastrocnemius, kidney, or heart of the oldest group of rats, and, in fact, the levels in the heart were significantly higher in the oldest age group when compared with the 13- and 23-month-old rats. These data agree with the decline in cyclic nucleotide phosphodiesterase activity observed in the cortex and striatum of aged animals.