Abstract Evidence suggests that in BALB/c mice infected with HSV-1, increased corneal scarring correlated with the presence of IL-12p40 mRNA in the cornea. To determine if this observed correlation reflected function, we have utilized mice with a homologous disruption of the gene encoding either the IL-12p35 subunit or the IL-12p40 subunit of IL-12. The severity of corneal scarring following ocular infection with HSV-1 was reduced significantly in naı̈ve IL-12p35- and IL-12p40-deficient mice compared with naı̈ve BALB/c mice, with the corneal scarring being low grade in the IL-12p35-deficient mice and completely absent in the IL-12p40-deficient mice. The reduction in the corneal scarring could not be attributed to a reduction in the HSV-1 titers in the eyes, which were not significantly different from the BALB/c mice, or to differences in the production of T H1 responses (IL-2 and IFN-γ production) by the infected mice. Taken together, these results suggest the importance of IL-12 in the induction of corneal scarring in HSV-1-infected mice.