Collecting skin biopsies from large whales for genetic analysis is often subject to national permit, and in the case of cow-calf pairs, it may be prohibited. We present results of 906 biopsy attempts on southern right whales (Eubalaena australis) in South African waters between 1995 and 1997, including 147 cow-calf pairs. Our sampling success was higher for biopsy darts with a bore of 4 mm compared to 4.6 mm. Contact periods averaged 17.7 min for cow-calf pairs and 25.4 min for whales unaccompanied by calves. There were no significant differences in the short-term reactions of males and females to biopsying, but the reaction of single animals of either sex was greater than for larger groups. Cows accompanied by calves had the strongest reactions, which were significantly greater than even single females. We found evidence of sensitization to repeat biopsying (over periods of hours to 65 days) for cows but not calves (n = 20). We compared the subsequent reproductive history of 117 biopsied cows with that of 163 unbiopsied cows from the same years, and we compared the distribution of calving intervals for biopsied animals with 829 intervals recorded from 1985 to 1995. We did not detect any adverse effects on the proportion of successful reproductive cycles, and hence calf survival, or the proportion of longer-than-normal cycles, although the power of all the statistical tests was low. We concluded that any prohibition on the biopsy sampling of cow-calf pairs should be carefully reconsidered in the light of the valuable genetic insights such sampling could achieve.