At a similar decrement in pH, acidosis produced by lowering the concentration of medium bicarbonate (metabolic acidosis) induces greater net calcium efflux from cultured neonatal mouse calvariae than acidosis produced by increasing the partial pressure of carbon dioxide (respiratory acidosis). This differential effect is due, at least in part, to enhanced cell-mediated bone mineral resorption during metabolic acidosis. To determine the effect of acidosis on osteoblastic bone formation we utilized primary cultures of neonatal mouse calvarial cells which produce calcified nodules in culture. Cells were plated at 4.5 x 10(4) cells/35 mm dish and incubated until confluent (day 9). Nodule formation was then induced by addition of beta-glycerophosphate and ascorbic acid and the cultures were randomly divided and then cultured in control (Ctl, N = 18) medium or in medium simulating metabolic (Met, N = 17) or respiratory (Resp, N = 19) acidosis. Medium was changed and calcium (Ca) measured every 48 hours until day 23. The mean initial medium pH of all Resp cultures (7.186 +/- 0.002) was lower than Met (7.243 +/- 0.006, P < 0.01), which was lower than Ctl (7.502 +/- 0.002, p < 0.01), yet the number of discrete nodules formed in Met (22 +/- 4 nodules/cm2) was lower than Resp (43 +2- 7, P < 0.01), and both were lower than Ctl (88 +/- 6, P < 0.01 vs. both Met and Resp).(ABSTRACT TRUNCATED AT 250 WORDS)