The transmissibility of the strain of influenza virus which caused the 1968 influenza pandemic is poorly understood. Increases in outbreak size between the first and second waves suggest that it may even have increased between successive waves. The authors estimated basic and effective reproduction numbers for both waves of the 1968 influenza pandemic. Epidemic curves and overall attack rates for the 1968 pandemic, based on clinical and serologic data, were retrieved from published literature. The basic and effective reproduction numbers were estimated from 46 and 17 data sets for the first and second waves, respectively, based on the growth rate and/or final size of the epidemic. Estimates of the basic reproduction number (R(0)) were in the range of 1.06-2.06 for the first wave and, assuming cross-protection, 1.21-3.58 in the second. Within each wave, there was little geographic variation in transmissibility. In the 10 settings for which data were available for both waves, R(0) was estimated to be higher during the second wave than during the first. This might partly explain the larger outbreaks in the second wave as compared with the first. This potential for change in viral behavior may have consequences for future pandemic mitigation strategies.