Relationships were examined between spatial learning and hippocampal concentrations of the alpha, beta(2) and gamma isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined for individual B-month-old (n = 13) and 24-month-old (n = 27) male Long-Evans rats trained in the water maze on a standard place-learning task and a transfer task designed for rapid acquisition. The results showed significant relationships between spatial learning and the amount of PKC among individual subjects, and those relationships differed according to age, isoform, and subcellular fraction. Among 6-month-old rats, those with the best spatial memory were those with the highest concentrations of PKC gamma in the particulate fraction and of PKC beta(2) in the soluble fraction. Aged rats had increased hippocampal PKCy gamma con centrations in both subcellular fractions in comparison with young rats, and memory impairment was correlated with higher PKC gamma concentrations in the soluble fraction. No age difference or correlations with behavior were found for concentrations of PKC gamma in a comparison structure, the neostriatum, or for PKC alpha in the hippocampus. Relationships between spatial learning and hippocampal concentrations of calcium-dependent PKC are isoform-specific. Moreover, age-related spatial memory impairment is associated with altered subcellular concentrations of PKC gamma and may be indicative of deficient signal transduction and neuronal plasticity in the hippocampal formation.