The Angelman syndrome (AS) and Prader-Willi syndrome (PWS) loci have been mapped to chromosome 15q11-q13. Chromosomal deletions of differing parental origin in the two syndromes have been interpreted as being due to genetic imprinting. Molecular analysis of patients with varying deletions has localized the AS locus to the interval between D15S113 and GABRB3 and the PWS locus between D15S13 and D15S113. In the present study, DNA cloning and physical mapping techniques have been used to characterize the AS/PWS chromosome region in the vicinity of D15S10, a locus that is telomeric to D15S113 and centromeric to GABRB3. A CpG island near TD3-21 at D15S10 has been cloned, allowing the identification of a widely expressed 4.5-kb transcript and providing a novel DNA marker, OP3, at this locus. OP3 and TD3-21 have been used to construct a long-range physical map extending over approximately 2800 kb. Clusters of rare-cutting restriction sites on this map locate four other CpG islands. Since these CpG islands lie within the minimum deletion intervals for AS and PWS, they mark the possible locations of candidate genes for the two syndromes.