This study was undertaken to investigate if dimethylsulfoxide (DMSO)-induced potentiation of maternal toxicity and teratogenicity of caffeine (CA) is mediated by DMSO-induced alteration of CA levels in maternal and fetal tissues. Pregnant CD 1 mice were given single dose of [14C]-caffeine intraperitoneally (i.p.) on gestational day 12, in distilled water (DW) or 20% (v/v) solution of DMSO in DW. At 6, 12, and 24 hr following dosing, radioactivity in various maternal and fetal tissues was compared. Significantly (P < or = 0.05) higher CA-derived radioactivity was seen in maternal brain, carcass and heart as well as placenta and fetal heads and bodies 6 hr after dosing with CA in DMSO compared to CA in DW. A concomitant reduction in urinary excretion of CA-derived radioactivity in DMSO group or compared to CA in DW was observed at this time. At 12 hr following dosing, significantly (P < or = 0.05) higher CA-derived radioactivity was noted in maternal heart, brain, and carcass; placenta; and fetal bodies in mice receiving CA in DMSO compared to those receiving CA in DW. These results suggest that increased accumulation of CA in certain maternal and fetal tissues could contribute to the observed increase in maternal and fetal toxicity of CA by DMSO.