Native and recombinant forms of transforming growth factor-beta 1 (TGF-beta 1) are synthesized predominantly as biologically latent complexes. Physicochemical analysis demonstrates that the more recently described TGF-beta 2 and TGF-beta 3 are also latent, and reveals a common series of sharply defined parameters for activation. Human recombinant latent TGF-beta's 1 and 2 show identical profiles of activation by acid and base; the transition from latency occurs between pH 4.1 and 3.1, and between pH 11.0 and 11.9. The profile for chicken recombinant latent TGF-beta 3 is slightly shifted with activation between pH 3.1 and 2.5, and between pH 10.0 and 12.3. Thermal activation of native and recombinant latent TGF-beta 1 occurs over the temperature ranges of 75-100 degrees C and 65-100 degrees C, respectively, with complete activation after 5 min at 80 degrees C. Temperatures above 90 degrees C result in thermal denaturation of TGF-beta 1 itself. Recombinant latent TGF-beta's 2 and 3 are also activated over this temperature range; however, maximum activation occurs at 100 degrees C. These results suggest common elements in latent complex structure despite differences between the TGF-beta subtypes in pro-region primary sequence.