Many diseases are characterized by inflammatory reactions involving both the innate and adaptive arms of the immune system. Thioglycolate medium (TM) injection into the peritoneal cavity has long been used as a stimulus for eliciting inflammatory macrophages for study and for determining the importance of a particular mediator in inflammation. However, the response to this irritant may not be relevant to many inflammatory diseases. Therefore, we have developed an Ag-specific peritonitis model using methylated BSA (mBSA) as the stimulus. Priming mice intradermally with mBSA in adjuvant and boosting 14 days later, followed by an i.p. challenge with mBSA after an additional 7 days, led to an inflammatory reaction equivalent in magnitude to that induced with TM as judged by the number of exudate cells. The inflammatory macrophages elicited by the mBSA protocol differed, being smaller and less vacuolated than TM-elicited macrophages. Also, macrophages from 4-day mBSA-induced exudates expressed more MHC class II than TM-induced exudates, were able to stimulate allogeneic T lymphocytes, and upon in vitro stimulation with LPS secreted greater levels of IL-6 and IL-1beta. Macrophages from 4-day TM-induced exudates, on the other hand, expressed Ly6C and ER-MP58, immature myeloid markers. The inflammatory response elicited using the Ag mBSA may be more relevant for studying the inflammatory responses in many diseases, such as those of autoimmune origin and those involving an acquired immune response.