Purified outer membranes from Neisseria gonorrhoeae strain M or B were prepared. Gonococcal outer membranes were pure as evidenced by banding in sucrose gradients at a density of 1.23 g/cm3, simple protein composition patterns when analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, low succinic dehydrogenase levels, and few precipitin peaks obtained in two-dimensional immunoelectrophoresis against hypcrimmune serum to gonococcal sonicates. Isolated outer membranes administered as antigen to guinea pigs produced strain-related protection against gonococcal infection in amounts <1% of the weight of whole gonococci required to produce comparable protection in chimpanzees. One-hundred percent (18 of 18) and 95% of con trol guinea pigs (19 of 20) were infected when challenged with M and B strain gonococci, respectively. In contrast, 26% (eight of 31) and 94% (16 of 17) of guinea pigs immunized with M strain outer membrane were infected when challenged with comparable inocula of M and B strain gonococci, respectively. Similarly, 25% (two of eight) and 100% (six of six) of animals immunized with B strain outer membrane were infected when challenged with comparable inocula of Band M strain gonococci, respectively. These results suggest that antigens capable of inducing strain-related protection to gonococcal infection are present within the gonococcal outer membrane.