OBJECTIVE: To determine whether the reduction in the protamine P2 content (increased P1/P2 ratio) reported in some infertile patients could result from incomplete processing of protamine P2 precursors. DESIGN: Analysis of samples with a marked reduction in the protamine P2 content using polyacrylamide gel electrophoresis and subsequent detection of protamine P2 precursors through Western blot analysis. SETTING: University departments and laboratories. PATIENT(S): One hundred eighty-four men undergoing an evaluation for infertility. MAIN OUTCOME MEASURE(S): Comparative Western blot analysis of nuclear sperm proteins using specific antibodies to protamine P1 and protamine P2. RESULT(S): After selection of the samples with a marked reduction of the protamine P2 content and subsequent analysis by Western blot, a small proportion of putative P2 precursors was detected in most samples, whereas a significant increase was detected in two of them. CONCLUSION(S): In some infertile men, a reduction in the protamine P2 content relative to protamine P1 (increased P1/P2 ratio) is detected concomitant with an increase in the amount of putative P2 precursors. This could represent the first report of incomplete processing of a nuclear sperm protein in humans.