The chick embryo was used to study the effects of neutral red (NR) on the frequency of sister-chromatid exchange (SCE) in specific tissues exposed to this mutagen for short and long periods as development proceeded. In short-term trials, aqueous NR at doses of 10, 25 and 100 micrograms was injected in 3-day and 6-day embryos. In each case, embryos were also treated with 5-bromodeoxyuridine (BrdU) for a 24-h period (two cell cycles) and harvested at 4 days and 7 days, resp. A long-term exposure (about 8 cell cycles) was achieved by exposing embryos to NR from day 3 to day 7 of incubation. At a NR dose of 25 micrograms, the chronic exposure resulted in a doubling of the rate of SCE (11.4/cell) over that observed in embryos exposed for only 24 h at either days 3-4 (6.0/cell) or days 6-7 (6.0/cell). At 100 micrograms of NR, the same relationship held with SCE rates of 14.2/cell for the chronic exposure versus rates of 8.0/cell (3-4 days) and 6.9/cell (6-7 days). At 10 micrograms of NR, no such accumulation of SCE occurred upon long-term treatment. These results show an enhanced SCE response upon growth of embryonic cells in the presence of NR for several days. This may be the result of the persistence of past lesions with the addition of more lesions upon continued exposure to NR.