Rationale: The relationships between allergen exposures, allergy and asthma are complex. High exposure levels to cat allergen are associated with IgG and IgG₄ specific antibody responses without sensitisation or risk of asthma, a process described as a 'modified Th2 response'. Attenuation of risk of allergy and asthma at high exposure levels has been reported in longitudinal studies of both childhood and occupational asthma. Objectives: To investigate, using an occupational model, the relationships between estimated exposure to aeroallergens, the production of specific IgE, IgG and IgG₄ antibodies and the prevalence of associated symptoms. Methods: Cross-sectional survey of employees exposed to rats at work on six pharmaceutical sites across the UK. 689 (89%) provided a blood sample and completed a questionnaire. Measurements and Main results: At highest exposure to rats there was an attenuation of the exposure response for sensitisation and symptoms. In contrast the frequency of individuals producing high quantities of specific IgG and IgG₄ increased with exposure intensity. Ratios of IgG₄/IgE were highest in those handling the greatest number of rats. Risk of developing work related chest symptoms was lower for those who produced both specific IgE and IgG₄ compared to those with specific IgE only. Conclusions: High exposure to rats is associated with lower rates of specific IgE and symptoms but an increased frequency of high specific IgG and IgG₄ production. Specific IgG₄ produced together with specific IgE may reduce the risk of developing work related chest symptoms compared to when specific IgE is produced alone.