This study evaluates the relationship between interviewer level of experience and the positive predictive value and cost of telephone screening of subjects for randomized clinical trials. This is a previously uninvestigated area. Respondents to advertisements for chronic depression treatment research received brief, semi-structured telephone interviews (N = 347) either by research assistants (RAs) or by a senior investigator (SI). Those who met criteria based on the phone interview were then interviewed in person using the SCID-P. The RAs did not significantly differ from the SI in the proportion of phone screen positives who were also SCID positive or the proportion of phone screen positives who were randomized. While the SI performed phone interviews significantly faster than the RAs, the SI's higher salary generated a phone screening cost per randomized subject 56% more than that of RAs. The results suggest that trained research assistants are more cost effective than senior investigators for initial screening of depressed patients for research protocols. Further studies are needed to determine whether the findings reported would generalize to other research settings or patient populations.