Objectives: To study the immunological and clinical effects of long term levamisole therapy in nephrotic children. Methods: The study included 24 children aged from 4-12 years (14 males and 10 females) who presented with nephrotic syndrome (8 with steroid-sensitive disease, 8 with steroid-dependent disease and 8 with steroid-resistant disease). The study also included 10 apparently healthy controls of matched age and sex. All patients and controls were subjected to the following immunologic studies: percentages of total T lymphocytes and their subsets including T-helper (CD4) and T-suppressor (CD8) cells, serum levels of interleukin-2 (IL-2), immunoglobulins (IgG, IgA, IgM and IgE), certain complement components (C3 and C1q) and circulating immune complexes (CICs) as well as lymphoblast transformation index (LTI). A follow up study of these parameters was done after 28 weeks therapy during which all the studied cases received cases daily prednisone for 4 weeks, followed by 24 weeks therapy with alternate day prednisone for the steroid-sensitive cases while both steroid-dependent and steroid-resistant cases received levamisole with concomitant prednisone therapy. Results: Alterations in the studied parameters and the effect of different therapeutic regimens on these alternations are detailed. Conclusions: We concluded that several immunologic alternations were found in childhood nephrotic syndrome. Data of the present study support the hypothesis that abnormal immunoregulation play a role in the pathogenesis of the disease. Also, the role of levamisole in the management of childhood nephrotic syndrome seems to be promising, and its restoration of normal lymphocyte number and function possibly helps to eliminate gradually the pathophysiological events leading to a nephrotic state. We advocate its use in cases with frequently relapsing disease, cases with steroid-dependent disease and/or those with steroid –resistant disease.