Effects of lathyrogens such as aminoacetonitrile (AAN), beta-aminopropionitrile (BAPN) and cysteamine--known inhibitors of cross-linking of collagen--on the mechanical strength of the periodontal ligament of the rat mandibular first molar were examined by measuring the ultimate load required to extract the tooth from its socket in the dissected jaw. Single injections of AAN (40 approximately 100 mg/100 g body weight) or of BAPN (100 mg/100 g body weight) caused significant decreases of the mechanical strength 24 h after administration of the drugs but that of cysteamine (30 mg/100 g body weight) did not. Significant correlations between the dose of AAN or of BAPN and the mechanical strength were found following daily administrations of the drugs for 5 days. The relative potency of AAN to BAPN was estimated to be 4.5 by a slope ratio assay. The rapid appearance and disappearance of the effect of lathyrogens on the mechanical strength of the periodontal ligament of the rat mandibular first molar provide further evidence that the turnover of the collagen in the tissue is fast. The half-time of collagen synthesis was estimated to be approximately 3 d.