Hagfish serum contains naturally-occurring agglutinins which react to different degrees with heterogenetic, but non-Forssman antigens on the erythrocytes of various vertebrates. These antibodies of generally low activity were found to reside in the macroglobulin (IgM) fraction, but became undetectable after heating serum at 56°C for 30 min. Specific production of antibodies against sheep erythrocytes was regularly inducible, given suitable tactics of immunization. Hagfish which received weight-adjusted dosages every 14 days over a 70-day period at 18° showed 2³- to 2⁵-fold rises in specific hemagglutination titers. Induced antibodies were heat stable and displayed a high degree of specificity for sheep cell antigens. Chromatographic and immunoelectrophoretic analyses showed the naturally-occurring and induced antibody activity to be limited to a major macroglobulin fraction similar to but distinguishable from the IgM of higher vertebrates. Hagfish, despite their ‘most primitive vertebrate” status, are capable of vigorous production of antibodies to at least certain cellular and soluble antigens. The extent of their immunogenetic library and immunologic memory invites further investigation.