This study determined the ontogenic changes in learning and hippocampal protein kinase C (PKC) in C57 and DBA mice. Mice were tested on the visible- or hidden-platform versions of the Morris water task starting at 17, 24, 31, or 60 days of age. Both strains learned to locate the visible platform at all ages. C57 mice learned to solve the hidden-platform task when they were 24 days old, whereas DBA mice never learned to solve this task. Using a [3H]-phorbol ester binding assay, the authors found that both strains had similar amounts of hippocampal PKC at 10 and 17 days of age but that C57 mice had significantly more PKC at 24, 31, and 60 days of age. Immunoblotting results revealed that C57 mice had more gamma-PKC, but not alpha-PKC, than DBA mice. Thus, the development of performance differences in spatial learning between C57 and DBA mice parallels the ontogeny of hippocampal PKC.