Although the constructs of social support and unsupportive social interactions are particularly salient to individuals with fertility problems, few studies have explored the relationship between unsupportive social interactions (USI), social support, and psychological adjustment in the context of infertility. The purpose of the present study was to examine the direct effects of IVF-specific Total and Distancing USI, as well as IVF-specific social support, received from one’s spouse, upon psychological adjustment over time, among a sample of women undergoing IVF treatment. USI are unsupportive or upsetting responses received from others about a stressful life event. Distancing is a category of unsupportive responses that represent behavioral or emotional disengagement. This study was a longitudinal design. Data were analyzed using hierarchical multiple regression models. Full IRB approval was obtained and participants were recruited from a large infertility clinic, with multiple offices in a metropolitan area. A total of 35 women completed measures of IVF-specific Total and Distancing USI received from a spouse, IVF-specific social support received from a spouse, overall psychological distress, positive mood, and demographics. Questionnaires were initially completed prior to each participant’s oocyte retrieval procedure, and then a second time approximately 12 weeks after the oocyte retrieval procedure. To determine if pregnancy status at Time 2 was associated with any of the independent or dependent variables, t-tests were conducted. Data analysis also included a series of regression analyses to determine whether after controlling for Time 1 levels of psychological adjustment, Time 1 IVF-specific Total and Distancing USI received from a spouse, as well as Time 1 IVF-specific social support received from a spouse, were predictive of psychological adjustment at Time 2. Results of t-tests that compared mean variable scores based on pregnancy status did not reveal any significant differences between participants who were pregnant and those who remained infertile at Time 2 (p > .05). Regression analyses indicated that after controlling for Time 1 levels of adjustment, Time 1 IVF-specific Distancing USI received from a spouse was a significant predictor of overall psychological distress at Time 2, δF(1, 32) = 5.08, p < .05, and showed a trend toward predicting positive mood at Time 2, δF(1, 30) = 3.53, p = .07. However, after controlling for Time 1 levels of adjustment, neither Time 1 IVF-specific Total USI received from a spouse, nor Time 1 IVF-specific social support received from a spouse were predictive of overall psychological distress or positive mood at Time 2. These results are consistent with those from another longitudinal study of women with fertility problems, which also indicated that Distancing type USI received from others at Time 1 are associated with significant changes in adjustment at Time 2. In addition, the current findings suggest that USI received from a spouse, and specifically Distancing type responses, play a relatively stronger role than social support received from a spouse in their associations with both overall psychological distress and positive mood. There was no indication that patterns of association between IVF-specific social support or IVF-specific USI, and adjustment would vary based upon whether or not the IVF attempt resulted in a pregnancy.