AbstractGraded dosages of the niacin antimetabolite 6‐aminonicotinamide (6‐AN) were incorporated in the culture media of explanted day 10 rat embryos or injected directly into amniotic cavities of day 15 embryos. Regardless of the route of administration the resultant decreased growth and abnormal development were related to the concentration of the antimetabolite. Culturing embryos for 22–26 hours with 5 to 20 μg 6‐AN progressively interfered with subsequent somite growth and cardiovascular function. Addition of nicotinamide (NAM) to the cultures prevented the deleterious effects of the antimetabolite. Following infra‐amniotic injections, 54 to 94% of the implantation sites given 10 to 100 μg 6‐AN exhibited resorbed fetuses or young with abnormal palates, brains, or eyes by day 21 of gestation. The types of defects found in the present study were similar to those observed following maternal treatment with 6‐AN. Direct applications of this teratogen to isolated or in utero rat embryos resulted in decreased growth, increased fetal death, and congenital abnormalities without significant changes in m