Elevations in hypothalamic-pituitary-adrenal (HPA) axis activity have been implicated in the origins and exacerbation of mental disorders. Several lines of investigation suggest HPA activity, indexed by increased cortisol, is elevated in patients with schizophrenia and other psychotic disorders. This study examined the relation of cortisol levels and longitudinal changes with psychotic outcomes in at-risk adolescents. Participants were 56 adolescents who met risk criteria for psychosis, namely, schizotypal personality disorder (n = 5), prodromal symptom criteria based on the Structured Interview for Prodromal Symptoms (n = 17), or both (n = 34). Of these, 14 subsequently met DSM-IV criteria for an Axis I psychotic disorder (schizophrenia, schizoaffective disorder, or mood disorder with psychotic features). Participants were assessed at baseline and then followed longitudinally. Salivary cortisol was sampled multiple times at initial assessment, interim follow-up, and 1-year follow-up. Area under the curve (AUC) was computed from the repeated cortisol measures. The findings indicate that at-risk subjects who subsequently developed psychosis showed significantly higher cortisol at the first follow-up, a trend at the 1-year follow-up, and a significantly larger AUC when compared to those who did not convert. A similar pattern of group differences emerged from analyses excluding those who may have converted prior to the 1-year follow-up. These findings converge with previous reports on HPA activity in psychosis, as well as theoretical assumptions concerning the effects of cortisol elevations on brain systems involved in psychotic symptoms. Future research with larger samples is needed to confirm and extend these results.