A single gene (Pm. i) that affects scrapie incubation period in mice has been identified. I/LnJ mice have a very long incubation period after inoculation of scrapie prlons (200-385 days) and NZW/LacJ mice have a short one (113 f 2.8 days).(NZW x I/Ln) Fl hybrid mice had incubation times of 223-c 2.8 days indicating longer incubation times were domlnant. Incubation periods in the backcross progeny of (NZW/LacJ x I/LnJ) Fl x NZW/LacJ segregated into two groups (64 mice, 130+ 1.1 d; 88 mice, 195 f 1.9 d) indicating single gene control. NZW/LacJ and 20 other inbred strains have the/VII-~’allele which is Identified gs a 3.8 kb Xbal fragment using a hamster PrP (prion protein) cDNA probe. IlLnJ and three other pm@ mouse strains have a 5.5 kb Xbal restriction fragment. Analysis of DNA from 68 backcross mice indicated Pm-i is tightly linked to Pm-p, the structural gene for PrP.