Premeiotic inactivation of duplicated sequences (the RIP phenomenon of Selker et al.) was studied by tetrad analysis using ectopic copies of am+ (coding for NADP-specific glutamate dehydrogenase) and a missense allele am3, coding for a distinctive form of the enzyme, at the normal locus. In duplication crosses either both gene copies were inactivated or neither. Two inactivated am3 derivatives were shown to have undergone methylation and numerous base-pair changes, reflected in losses and gains of restriction sites, but without sequence rearrangement. Cutting at restriction sites within the disrupted sequences was incomplete but became almost complete following growth in the presence of 5-azacytidine. In a triplication cross in which one parent carried two unlinked ectopic gene copies together with am3 at the normal locus, premeiotic inactivation, when it occurred, tended to affect two of the three copies in any one ascus, but there were a few asci in which all three were inactivated.