The epitopes (antigenic determinants) evoked by guinea pig or monkey myelin basic protein (BP) for 7 monoclonal antibodies (MAb) have been localized to 4 different sequences of the BPs extracted from various species. The first pair of epitopes is included within residues 1-14 and reacts with 2 rat IgG MAbs having slightly different specificities. The second pair of epitopes overlap within the sequence 86-100, requiring the Phe(91)-Phe(92) residues. One includes only residues 90-100 and reacts with a rat IgG MAb, the other is longer and reacts with a mouse IgM MAb. The third epitope lies within residues 114-124 (specifically including the single Trp) and reacts with a rat IgG MAb. A cross-reacting epitope in the amino half of the molecule is present in certain species (human, bovine and guinea pig). The fourth pair of epitopes includes residues 131-140 and is severely species-restricted. A mouse IgM MAb reacts practically only with guinea pig BP. Another IgG MAb reacts with human, chimpanzee, monkey, bovine and rat-18.5 kDa BPs, to a much lesser extent with rabbit and rat-14 kDa BPs and not with guinea pig, pig or chicken BPs. A cross-reacting epitope in the amino half of the molecule may be present in the more reactive species.