Soluble non-cross-linked peptidoglycan polymers are released by gram-positive bacteria when beta-lactam antibiotics are administered to humans. In this report, we show that this type of peptidoglycan can stimulate monocyte-macrophage functions that cause inflammation. Non-cross-linked peptidoglycan polymers from penicillin-treated Streptococcus faecium were purified and shown to stimulate the production of interleukin 1 by human monocytes and of colony-stimulating factors by a murine macrophage cell line. In addition, the release of plasminogen activator by human monocytes was inhibited by the soluble peptidoglycan. These in vitro results suggest that prolonged treatment with beta-lactam antibiotics, by causing the production of soluble peptidoglycan, may result in interleukin 1-mediated inflammatory reactions, excessive production of monocytes and granulocytes, and increased fibrin deposition.