In this investigation of immunotherapy (IT) children 6-16 years old with rhinoconjunctivitis due to birch polli­nosis were included. I. Methodological studies. To monitor IT a reliable provocation test is desirable. The conjunctival provocation test (CPT) was evaluated in 20 children with four repeated challenges. The test was found to have a good preci­sion, it was simple and appeared to be clinically safe. After repeated tests the levels of IgE antibodies against birch increased considerably in three children, indicating an immunological response. A pollen peak affects the symptoms of an atopic individual for several days. Thus pollen counts for previous days must be taken into account when relating symptom scores with the counts. A dynamic time series model was therefore developed by which groups of atopic patients could be compared when exposed to different amounts of pollens. II: Cross-reactivity between deciduous trees during IT. Immunotherapy with pollen allergen preparations made from either birch (B) or a mixture of birch, alder and hazel (M) were compared. As measured with symptom scores the children in the M group improved at least as much as those in the B group. In the B group but not in the M group the improvement correlated with immunochemical findings before IT or early during the treatment, probably an unsignificant finding. Otherwise there was little difference between the two groups. Analysis of sera with crossed radioimmunoelectrophoresis in 20 children revealed that 60% of the children below 13 years had de­veloped IgE antibodies during IT against allergens against which they had not been allergic before IT. This had no appearent clinical implications. III: Oral immunotherapy (OIT). A pilot study of 18 children treated with high doses of a birch pollen allergen preparation in enteric coated capsules and 8 untreated controls indicated that OIT was effective as shown by lower symptom scores, less conjuctival sensitivity and increased levels of IgE antibodies against birch. However, the gastrointestinal side-effects were pronounced. Therefore a second double-blind study, in 30 children, was performed reducing the side-effects through a different dose schedule. Compared with the placebo group, the ac­tively treated children had lower symptom scores (p = 0.04), reduced skin sensitivity (p = 0.01), increasing levels of IgE (p = 0.001) and IgG (p = 0.007) antibodies against birch before the birch pollen season and a suppression of the seasonal increase in levels of IgE antibodies against birch (p <0.001). After three months of OIT but not after ten months they also had a lower sensitivity in CPT than the controls (p = 0.01). The intestinal permeability as assessed by the urinary recovery of differently-sized polyethyleneglycols was studied in 24 of the children during IT. No changes were seen in the group of actively treated children. In two ad­ditional children openly treated with OIT small bowel biopsies were taken with normal morphological findings. Thus OIT did not result in a generalized inflammation of the small bowel. / digitalisering@umu