Lauren, Maybe one of the vets will respond here, but from what I've seen, ferrets will usually not have a reaction to the first shot. It does seem to sensitize a few such that the will have a reaction on the second, third or fourth. If they don't have a reaction by the fourth, the incidence seems to go down, but I doubt if the risk ever goes entirely away. From my own experience it seems that the second and third vaccinations have the highest incidence of reactions. I personally favor separating the distemper and rabies vaccinations. That's a lot of load to put on one small animal at one time. We do premeditate with pediatric benadryl an hour before the vaccination and stay 30 minutes after the vaccination. We've seen reactions begin 20 minutes afterward, although most are within minutes. Dick B. [Posted in FML issue 1409]