Experimental autoallergic sialadenitis (EAS) in the LEW rat is an autoimmune lymphocytic destruction of the submandibular gland (SMG) induced by sensitization with an SMG homogenate emulsified in adjuvant. Here we report that the antigens in the SMG homogenate involved in the induction of EAS can be localized to both cell-surface and intracellular particulate fractions. Differential centrifugation procedures were used to isolate 10,000g, 25,000g, 40,000g, and 100,000g particulate fractions from the SMG of LEW or WF rats. The particulate SMG fractions were used to sensitize female LEW rats for EAS induction. Since the protein concentrations of the fractions varied as a percentage of their composition in the whole homogenate, additional experiments were performed using equivalent protein concentrations for sensitization. Two weeks after sensitization, the SMGs of the sensitized animals were recovered and processed for histologic examination. Samples of the SMG fractions used for sensitization were also examined by electron microscopy. The 25,000g and 100,000g fractions consistently induced extensive mononuclear cell infiltrates and exocrine gland destruction in the SMGs while the 10,000g and 40,000g fractions caused infrequent and minimal inflammatory cell infiltrates in the glands. These data, combined with the electron microscopic analysis of the fractions, suggest that the target antigens in EAS reside on particulate fractions from the SMG that have the characteristics of the cell surface (25,000g) and microsomes (100,000g).