The effect of H2 and non-H2 genes in a mouse model of protective immunity against Onchocerca lienalis microfilariae have been investigated. Non-H2 effects were determined using CBA, BALB/c, B10, SJL and TO strains. All were permissive for establishment of a primary infection with microfilariae, although significant differences in parasite recoveries were evident amongst the various strains. The effect of H2 genes upon a primary infection was investigated using H2 congenic B10 and BALB strains, B10, B10.S, B10.BR, B10.D2/n, BALB/c, BALB.B, and BALB.K. Significant H2 effects were seen among the relatively weak responder B10 strains, but were not present among the relatively strong responder BALB strains. These results support a dominant effect of non-H2 genes following primary exposure to microfilariae, and a 'fine tuning' effect of H2 genes that is apparent only in weaker responding strains. Upon reinfection of all the strains investigated, a gradation of protection was detected that appeared to be exclusively dependent upon H2.