Increased slow-wave sleep accompanies influenza infection in C57BL/6 mice but not BALB/c mice, These strains of mice possess different alleles of the genetic locus If-1, which codes for high (If-1(h); C57BL/6) and low (If-1(1); BALB/c) production of interferon (IFN), a putative sleep-inducing cytokine, To evaluate the contribution of the If-1 gene to differences in murine sleep propensity, sleep patterns were evaluated in mice treated with the IFN inducers polyinosinic:polycytidilic acid (pIC) or Newcastle disease virus (NDV), with influenza virus, or with murine interferon (IFN-alpha) or IFN-alpha/beta. As compared with baseline values, C57BL/6 mice exhibited increased slow-wave sleep after all three challenges, but BALB/c mice did not, Congenic B6.C-H28(c) mice, which bear the BALB/c allele for low IFN production on the C57BL/6 genetic background, showed enhanced slow-wave sleep after influenza infection but not after NDV, Exogenous IFN did not enhance slow-wave sleep in either C57BL/6 or BALB/c mice, These data suggest that the If-1 allele may influence the somnogenic responsiveness of mice under some conditions but that additional mechanisms may contribute to sleep enhancement during infectious disease.