IP (in McK 30830) is an inherited highly pleomorphic disease associated with central nervous system disorders in 30% of cases. It is transmitted in an X-linked dominant fashion with prenatal lethality in affected males. To date, we have used 17 probes to study genomic digests from members of a 3-generation pedigree which contains 13 potentially informative meioses. Informative polymorphisms were detected with five probes. Arranged from proximal to distal Xp, they are: p58-1 (which maps to Xp11←cen); OTC(Xp21); 754(Xp21.1←XP21.2); pERT87-15(Xp21) and dic56(Xp22←Xpter). When we examined the segregation of these multiple loci with the IP phenotype we observed one instance of double recombination, 8 simple recombination events and 4 instances of no recombination. For p58-1 we documented 2 recombinants with respect to IP in 11 meioses (2/11). The values for the other markers were: OTC, 5/13; 754, 6/12; pERT87-15, 7/12 and dic56, 9/13. These data suggest that IP locus is in or below Xp11, and are consistent with the cytogenetic assignement of IP to Xp11 on the basis of IP patients who carry Xp11-autosome translocations (Hodgson et al. (1985) Hum. Genet. 71:231-239).