T-lymphocyte dependence of the production of in vitro bone resorbing activity was examined using athymic (nu/nu) and euthymic (nu/+) mouse splenic leukocytes. Conditioned medium (CM) from unstimulated splenic leukocytes of nu/nu mice had greater in vitro bone resorbing activity compared to CM from nu/+ mice (1.7- as compared to 1.2-fold increase of 45Ca release in mouse calvaria). CM from concanavalin A (Con A)-treated nu/nu and nu/+ leukocytes had 1.8-fold and no increase in 45Ca release, respectively. CM from both nu/nu and nu/+ phytohemagglutinin (PHA)-treated leukocytes had a 1.7-fold increase in 45Ca release. Bone resorbing activity from nu/nu CM was inhibited by interferon-tau (10 & 100 IU/mL) and indomethacin (2 x 10(-6) M). CM (untreated or Con A-treated) from nu/nu leukocytes had higher levels of prostaglandin E (PGE) as compared to CM from nu/+ leukocytes, and indomethacin decreased PGE levels in nu/nu CM. Leukocytes from nu/+ mice had increased mitogenesis when stimulated with PHA (1, 3, & 10 micrograms/mL) or Con A (1 and 10 micrograms/mL), whereas leukocytes from nu/nu mice were nonresponsive or had significant inhibition of mitogenesis with PHA and Con A.(ABSTRACT TRUNCATED AT 250 WORDS)