Comorbid substance use and posttraumatic stress disorders (SUD-PTSD) predict poorer treatment outcomes. Self-medication has been forwarded as a symptom-level explanatory model. However, research has yet to be conducted that can provide detailed examination of SUD and PTSD symptom fluctuations over time as posited by such a process. This pilot study examined associations between PTSD and substance dependence (SD) symptoms/substance use using two established methodologies that assess week-by-week symptom and substance use/dependence status. Outpatients (N=35) in SUD treatment completed the Longitudinal Follow-Up Evaluation and the Time Lime Follow-Back Interview, retrospectively reporting weekly PTSD and SD symptoms, and substance use over the previous 6-months. Results indicated that weekly PTSD symptom fluctuations were concurrently associated with the presence of alcohol and cocaine dependence symptoms and were associated with the presence of opiate dependence symptoms in the following week. These findings support a self-medication conceptualization, underscore the utility of using a more detailed process analysis of PTSD and SD symptoms, and suggest that PTSD fluctuations are associated with substance problems, rather than with substance use per se.