Short-term (96-h) tests on Xenopus laevis embryos are advocated for rapid screening of teratogens, as an alternative to the use of mammals. The objective of the present investigation was to determine whether extending the short-term tests beyond 96 h would detect the teratogenicity of chemicals that would otherwise be missed by the short-term tests. Lead teratogenicity was examined in Xenopus, using lead concentrations of 0.02, 0.05, 0.1, 0.5, 1.0, and 3.0 mg/L, which bracket the U.S. Environmental Protection Agency (EPA) maximum allowable concentration of 0.05 mg/L in water. Short-term exposure times were 72 or 96 h, starting on d 1, 2, or 3 postfertilization, while long-term exposure covered d 1 through metamorphosis. Short-term exposure resulted in neural tube defects (when exposure included d 1 and/or d 2) and tail curvatures, but only at the higher lead concentrations (1 and 3 mg/L). Lower lead concentrations produced no malformations upon short-term exposure, and this corresponded with the absence of tissue lead uptake. On the other hand, long-term exposure to lead (> 3 wk) resulted in the delayed appearance of lordoscoliosis at low lead concentrations (0.02-0.1 mg/L). The delayed appearance of lordoscoliosis corresponded roughly with the attainment of stable lead tissue levels, and this malformation persisted after metamorphosis. Thus, short-term observation tests alone may fail to detect the teratogenicity of low concentrations of environmental chemicals, and may result in the setting of inappropriately liberal exposure standards.