Objective: This study tested a multilevel biobehavioral family model proposing that negative family emotional climate contributes to child depressive symptoms, which in turn contribute to asthma disease severity. Parent-child relational insecurity is proposed as a mediator. Method: Children with asthma (N = 112; ages 7-18; 55% male) reported relational security, anxiety, and depressive symptoms. Parent(s) reported demographics, asthma history and symptoms, and family emotional expression. Asthma diagnosis was confirmed by medical history provided by parent and child together, clinical evaluation, pulmonary function tests, and methacholine challenge, with disease severity categorized by National Heart, Lung, and Blood Institute guidelines. Medication adherence was measured prospectively. Results: Path analysis indicated a good fit of data to the hypothesized model (chi square [subscript 2] = 0.072, p = 0.97, normal fit index = 0.998, root mean square error of approximation = 0.000). Negative family emotional climate predicted child depressive symptoms (beta = 0.21, p less than 0.04), which predicted asthma disease severity (beta = 0.35, p less than 0.001), with relational insecurity a partial mediator (beta = -0.23, p less than 0.05, beta = 0.46, p less than 0.001, respectively). Depression was associated with disease severity even after controlling for adherence (r[subscript p] = 0.38, p less than 0.05). Conclusion: Findings are consistent with the proposed family model, suggesting the clinical importance of assessing and intervening in these specific family relational processes when treating children with depression and asthma. (Contains 2 figures and 2 tables.)