A low level of response (LR) to alcohol (i.e., the need for higher amounts to have an effect) is a genetically influenced characteristic that is both found in populations at high risk for future alcoholism and that predicts alcohol-related life problems in the future. A simple paper-and-pencil test that asks subjects to estimate the number of drinks required to produce each of four effects at different times in their lives, the Self-Rating of the Effects of Alcohol (SRE) questionnaire, was developed to facilitate studies of LR. However, data to date on this indirect measure of LR have focused primarily on young male populations. The current study reports SRE values from 121 middle class, middle-aged women who were selected because they were married to men who participated in a longitudinal study of sons of alcoholics and controls. As predicted, the SRE measure of LR, which records the perceived responses of alcohol early in the drinking career (FIRST 5), correlated significantly with recent drinks per drinking day (0.18, p < 0.05), a diagnosis of an alcohol use disorder (0.33, p < 0.001), and with a family history of alcohol dependence (0.20, p < 0.05). The LR value from the SRE reflecting the perceived number of drinks required for effects in the most recent 3 months correlated more closely with both quantity and frequency of drinking (0.36 and higher, p < 0.001), and related to recent nicotine use (0.23, p < 0.05). These data indicate the potential usefulness of the SIZE as a measure of LR as a risk factor for alcoholism in relatively highly functioning middle-aged women.