Research on the Maudsley Reactive and Maudsley Nonreactive strains conducted primarily between 1980 and 2001 is reviewed. One line of research, which has found consistent differences between the Harrington derivation of the Maudsley Reactive (MR/Har) and Maudsley Nonreactive (MNRA/Har) strains in conflict situations, appears to support the traditional view of the two strains as representing models of global differences in emotionality. In contrast, comparisons of the two strains in two commonly used tests that involve a component of fear either do not reveal differences between the strains (escape-avoidance conditioning) or are inconsistent in expression (elevated plus maze). Emphasis is placed on the importance of recognizing that most of the phenotypic differences discovered among selected inbred strains, including the Maudsleys, will inevitably be unrelated to the original selection criterion, but that many of these phenotypic differences will have their own intrinsic interest. For example, the fact that, relative to MNRA/Har, two bottle ethanol preference is greater in MR/Har rats and that MR/Har rats exhibit greater exploration of novel stimuli when these are presented in a familiar environment may have little to do with the hypothesized differences in emotionality among the strains. It is suggested the MR/Har drinking pattern in alcohol preference tests, which is characterized by considerable variability, may complement other models of alcoholism, especially in the investigation of environmental influences which contribute to the variability. In the case of strain differences in response to novelty, this may help explain some of the inconsistencies in findings in the elevated plus maze, which, aside from provoking fear, also contains an important element of novelty. Finally, it has been found that alterations in the peripheral sympathetic nervous system (PSNS) are correlated with strain differences in open-field defecation (OFD) in the Maudsley model, and it has been proposed that the lower OFD of MNRA/Har rats is a direct result of sympathetic inhibition of colonic motility. These strain differences in the PSNS are furthermore associated with important alterations in the response of the central noradrenergic system to acute and chronic stress. It is hypothesized that genes may have influenced PSNS tone by altering CNS structures with descending projections. If the link between low levels of OFD and higher peripheral sympathetic tone is supported by additional experiments, this will force reconsideration of OFD as an index of emotionality.