Previous studies have shown that interleukin-1 beta (IL-1 beta) is a potent bone resorption stimulating agent in cultures of fetal or neonatal bones. In the present study, evidence has been provided showing that this cytokine failed to stimulate bone resorption in cultured 75-day-old mouse calvaria maintained in a chemically defined medium for 14 days, as determined by measuring calcium release into the medium and histological examination of cultured bones. Moreover, the cytokine significantly inhibited basal bone resorption in cultured 75-day-old mouse calvaria, a finding reminiscent of the paradoxical effect observed with 1 alpha,25-dihydroxycholecalciferol. Since IL-1 beta did not alter the number of osteoclasts present in the cultured older calvaria as compared to the untreated control, we hypothesized that in such cultured older bones the cytokine affects primarily the function rather than proliferation/differentiation of osteoclasts, either directly or indirectly through its action on other cells in bone tissue, such as osteoblasts or stromal cells. Also, it is possible that the cytokine affects the formation and/or function of macrophages that have been shown to participate in the bone resorption process. These findings support the concept that at different stages of host maturation, bone tissue may exhibit a different response to the same osteotropic agent.