There are few empirical data to support the widely accepted practice of screening depressives for causative thyroid disease, as summarized in the previous article of this series. We therefore formed, as a null hypothesis, the proposal that ambulatory depressives do not comprise an enriched sample for unsuspected clinical hypo- or hyperthyroidism. To investigate this issue we studied a prospectively assessed sample of 166 consecutive medically healthy outpatients who a) met criteria for a current major depressive episode and b) underwent thyroid function testing consisting of determination of serum total thyroxine (T4) and free thyroxine index (FTI); 105 of the 166 patients also had thyrotropin (TSH) determination. Laboratory thyroid testing was mandated by drug treatment protocol and was therefore not influenced by clinician-related testing factors. The clinic did not participate in thyroid related research and therefore was not likely subject to thyroid related patient selection or referral bias. Caseness was defined by abnormal FTI confirmed by subsequent testing. Prevalence rates for abnormal total T4 and TSH were also calculated. Only one case (0.6%) of hypothyroidism and no cases of hyperthyroidism were found. Four patients (2.4%) had decreased total T4 but normal FTI while two (1.2%) had high total T4 with normal FTI. Elevated TSH was found in only two (1.9%). Thus prevalence of hypo- or hyperthyroidism in patients with major depressive disorder does not differ from that reported for the general population. These data indicate that thyroid screening guidelines which have been developed for the general population may therefore be preferable to routinely screening all ambulatory depressives. A strategy for testing ambulatory depressives is suggested: That all ambulatory depressives be routinely screened for signs, symptoms, and specific risk factors for hyper or hypo-thyroidism, but that routine junction testing is not indicated. Depression 1:220–224 (1993). © 1993 Wiley-Liss, Inc.