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Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty. Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1,8 and the IL-1 receptor antagonist (IL-lra) in human peripheral blood mononuclear cells. Live B. burgdorferi induced fivefold more IL-1l@ than IL-la and sevenfold more IL-1l8 than IL-lra; LPS or sonicated B. burgdorferi induced similar amounts of all three cytokines. This preferential induction of IL-1,B was most dramatic in response to a low passage, virulent preparation of B. burgdorferi vs. three high passage avirulent strains. No difference in induction of IL-lra was seen between these strains. The marked induction of IL-1iB was partially diminished by heat-treatment and abrogated by sonication; ILlra was not affected. This suggested that a membrane component(s) accounted for the preferential induction of IL-1i6. However, recombinant outer surface protein ,B induced little IL-1i6. burgdorferi-induced IL-1A6 mRNA showed biphasic elevations at 3 and 18 h. B. burgdorferi-induced IL-lra mRNA peaked at 12 h, whereas LPS-induced IL-lra mRNA peaked at 9 h. 8 synthesis increased in response to increasing numbers of spirochetes, whereas IL-lra synthesis did not. The preferential induction by B. burgdorferi of IL-1i8 over IL-lra is an example of excess agonist over antagonist synthesis induced by a microbial pathogen, and may contribute to the destructive lesion of Lyme arthritis. (J. Clin. Invest. 1992. 90:906-912.)