In a human challenge experiment, the infectivity of gonococci with sialylated lipooligosaccharide (LOS) was compared with the infectivity of gonococci with unsialylated LOS. Volunteers were intraurethrally inoculated with approximately 5000 sialylated or unsialylated piliated, non-opaque (P+Opa-, transparent) colony type gonococci, strain MS11mkC. Five (83%) of 6 volunteers inoculated with unsialylated gonococci became infected; however, only 1 of 5 volunteers became infected with sialylated gonococci. The unsialylated gonococcal infections, with a median incubation time of 62 h (range, 32-98), were similar to previously described experimental infections. Gonococci shed by infected volunteers showed a transition from the P+Opa- phenotype of the inoculation strain to the P+Opa+ (piliated, opaque) phenotype 12-60 h before onset of disease. The subject with sialylated gonococcus infection had an extended incubation period, showing a progressive increase in the number of organisms shed until he became symptomatic on day 6 after inoculation. These results show that gonococci with sialylated LOS are less infective than gonococci with unsialylated LOS.