The sera of vasectomized men and of patients with immune infertility were used to study the antigens and epitopes of sperm nuclear proteins that bind antibodies in these sera. No reaction with sperm histones was observed except for one serum. P1, P2 protamines and pro-P2 protamines were recognized by auto-antibodies. Studies with peptides derived from P1 and P2 protamines and with mammalian protamines related to HP1 showed that antibodies are mainly specific for a folded protamine molecule, more especially antibodies from vasectomized men. These results disagree with the random coil model proposed for protamines by several previous works. A cross-reactivity between P1 and P2 protamines was observed only for the whole molecules and not for peptides derived from them. This observation suggests that the two classes of protamines, different in sequence, may have a similar folding and thereby may be functionally equivalent.