Calmodulin contents of normal rat liver, host liver [bearing hepatoma 5123t.c.(h)], regenerating liver, and Morris hepatomas 7800, 5123t.c.(h), and 7794A were determined by phosphodiesterase assay and by radioimmunoassay. The calmodulin levels determined by both assays were significantly increased in three hepatomas when compared to the corresponding values of normal liver. The order of increase in calmodulin content was as follows: normal liver = host liver less than 7794A (slow growth rate) less than 5123t.c.(h) (intermediate growth rate) less than 7800 (fast growth rate). In regenerating liver (24 hr after partial hepatectomy), the calmodulin content was not different from that of normal liver. In good agreement with the literature, the calmodulin values measured by the phosphodiesterase assay were always lower than those determined by radioimmunoassay. Calcium and magnesium contents were measured by atomic absorption spectrophotometry in acid digests of these tissues. Both cation contents were significantly increased in the three hepatomas studied when compared to the corresponding values of normal liver; the extent of increase for calcium content (120 to 240%) was much greater than that for magnesium (30 to 40%). The order of increase for both cations was as follows: normal liver = host liver less than 5123t.c.(h) less than 7794A less than 7800. Therefore, there does not appear to be any correlation between the cation contents and hepatoma growth rates. In regenerating liver, magnesium content was about 14% higher than that of normal liver. In summary, the results indicate that only the increase of calmodulin appears to correlate positively with the growth rate of these tumors. This correlation suggests that calmodulin may be involved in tumor cell growth regulation.