The important role of genetic factors in the mediation of sensitivity to pain and pain inhibition is being increasingly appreciated. In an attempt to systematically study the genotypic influences on inflammatory nociception, we conducted a survey of the nociceptive responsivity of three common outbred mouse strains and 11 inbred mouse strains on the formalin test. The formalin test is known to display a biphasic temporal pattern of behavioral and electrophysiological activity, defined by an acute/early phase and a tonic/late phase. Nociceptive sensitivity (licking/biting of the affected area) to a subcutaneous injection of 5% formalin (25 microl volume) into the plantar surface of the right hindpaw displayed moderate heritability in both phases (0.38 and 0.46, respectively). One strain, A/J, was identified as extremely resistant to formalin nociception, displaying total licking in the acute and tonic phases that was 60% and 87% lower, respectively, than the grand mean of all strains. A subsequent series of experiments were performed to characterize the difference between A/J and C57BL/6J mice. The findings establish this inbred strain comparison as a useful genetic model of nociceptive sensitivity.