Background B cells undergo maturation and class-switching in response to antigen exposure and T-cell help. Early B-cell differentiation has not been defined in patients with early-onset atopic dermatitis (AD). Objective We sought to define the frequency of B-cell subsets associated with progressive B-cell maturation and IgE class-switching. Methods We studied 27 children and 34 adults with moderate-to-severe AD (mean SCORAD score, 55 and 65, respectively) and age-matched control subjects (15 children and 27 adults). IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometric panel were used to determine the frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgE) levels were measured by using ImmunoCAP. Results Compared with adults, children showed T-cell predominance in the skin. Circulating CD19+ CD20+ B-cell counts were lower in patients with pediatric AD than in control subjects (24% vs 33%, P  = .04), whereas CD3+ T-cell counts were higher (62% vs 52%, P  = .05). A decreased B-cell/T-cell lymphocyte ratio with age was observed only in pediatric control subjects ( r  = −0.48, P  = .07). In pediatric patients with AD, a positive correlation was observed between B-cell/T-cell ratio and nonswitched memory B-cell counts ( r  = 0.42, P  = .03). Higher frequencies of positive sIgE levels were seen in pediatric patients with AD ( P  < .0001). Diverse sIgE levels correlated with SCORAD scores and age of pediatric patients with AD ( P  < .01). Positive correlations were observed between activated B-cell and memory T-cell counts ( P  < .02). In patients with AD, IgE sensitization to most allergens clustered with age, TH 1, TH 2, total IgE levels, and B-cell memory subsets. Conclusions Peripheral B and T cells are altered in pediatric patients with early AD, but T cells predominate in skin lesions.