The virulence of lipopolysaccharide (LPS) variants of Neisseria gonorrhoeae strain Gc40 was studied in vivo using the guinea-pig subcutaneous chamber model. Survival of variants D1, D2, D4 and D5 was assessed by viable counts made on chamber fluid at various times after inoculation. Chemotactic effect was measured by counts of white cells in the chambers. Differential cell counts and assessments of the location of the gonococci were made on Giemsa-stained smears of chamber fluid. Sensitivity of the variants to normal guinea-pig serum was determined by in vitro bactericidal assays. D1 and D5 had relatively high Mr LPS which was shed in the medium, were serum resistant, produced intense infections and were mainly extracellular. Large number of damaged white cells were present. D2 and D4, had low Mr LPS which was poorly shed in the medium, were serum sensitive and produced low grade infections. D2 was the least infective and was seen mainly inside neutrophils. Collectively the data indicates that the type of LPS on the gonococcal surface and possibly the amount of shed LPS strongly influence the fate of gonococci in vivo, in an environment in which antibodies, complement and phagocytic cells are freely available. This may be decisive at some stages of the human infection.