Since meniscal healing is region-specific, we studied the regional (peripheral compared with central) response of meniscal explants to human, recombinant platelet-derived growth factor-AB. Meniscal explants from the hindlimbs of both knees of mature sheep were sectioned and were cultured with variable doses of human, recombinant platelet-derived growth factor-AB, and incorporation of [3H]-thymidine was measured. The mitogenic response was measured at different times in culture (48 or 96 hours) and by location (lateral or medial). In the absence of the growth factor, the peripheral third of both menisci incorporated 10-fold more [3H]-thymidine on a weight basis than did the central two-thirds. Cellularity was equivalent in the two regions. Doses of less than 100 ng/ml of growth factor produced either no stimulation or a variable response. A dose of 100 ng/ml resulted in consistent, significant (p < 0.05) stimulation in all groups in the peripheral region, and a dose of 200 ng/ml provided more than a 2.5-fold increase. Multiple-factor analysis of variance demonstrated that there were no significant differences between experiments, times in culture, or menisci. The central region did not respond to stimulation with the growth factor at any of the doses tested. These data suggest that regional differences (peripheral compared with central) in responsiveness to human, recombinant platelet-derived growth factor-AB may reflect a different level of signal transduction machinery for growth factor receptors and distinct fibrobchondrocyte populations. These findings are consistent with the variable healing capacity of the meniscal regions in vivo and suggest a pharmacological means to promote the repair of the peripheral meniscal region.