Allergic rhinitis (AR) and allergic asthma (AA) are characterized by T helper (Th)2-polarized immune response. Soluble human leukocyte antigen G (sHLA-G) molecule plays an immunomodulatory activity. Previously, it has been reported that children with AR or AA had higher sHLA-G levels in comparison with normal subjects. Thus, the present study aimed at confirming these data in adults and investigating whether there was a relationship between serum sHLA-G levels and serum IgE levels, in patients with AR or AA. One hundred twenty symptomatic patients, suffering from respiratory symptoms, were enrolled: 45 non-allergic and 75 allergic. A group of 44 healthy subjects was considered as control. Serum sHLA-G levels and serum allergen-specific IgE were determined by immunoenzymatic methods. Allergic patients had significantly higher levels of sHLA-G molecules than non-allergic patients and normal controls (p<0.0001). There was no difference between AR and AA. sHLA-G moderately related with allergen-specific IgE both in AR (r=0.468) and AA patients (r=0.479). The present study confirms that serum sHLA-G molecules are significantly increased in allergic disease and demonstrates that sHLA-G levels are related with allergen-specific IgE levels.