Background Risk of indoor exposure to volatile organic compounds of purported microbial origin on childhood symptoms of wheezing, rhinitis, and/or eczema, and doctor-diagnosed asthma, rhinitis, and eczema, respectively, remain unclear. Objective To test hypotheses that total sum of 28 microbial volatile organic compounds (Σ26 MVOCs): 1) poses independent risk on doctor-diagnosed asthma, rhinitis, and eczema, respectively, as well as multiple symptom presentation with a minimum of the two of the above conditions (i.e. case); 2) is associated with significant interaction with absolute humidity (AH) on additive scale. Methods In a case-control investigation, 198 cases and 202 controls were examined during November 2001 – March 2002 period through home indoor air sampling, air quality inspection, and health outcome ascertainment. Results Not only the Σ28 MVOCs but also the global MVOC index were significantly higher within the homes of the cases with a high AH, compared to the controls with a low AH (all Ps < 0.001). Only the cases, but not the controls, were associated with a dose-dependent increase in the exposure variables of interest (Σ28 MVOCs) per quartile increase in AH (P < 0.0001 for the cases; P = 0.780 for the controls). Only among the children who live in a high AH homes, a natural log (ln)-unit of Σ 28 MVOCs was associated with 2.5-times greater odds of the case status (95% CI, 1.0–6.2; P = 0.046), compared to 0.7-times the odds (95% CI, 0.4–1.0; P = 0.074) of the same outcome among the low AH homes. Specifically, joint exposure to a high MVOCs and high AH was associated with 2.6-times greater odds of the doctor-diagnosed asthma status (95% CI, 0.7–8.91; P = 0.137). Conclusion Joint occurrence of high Σ28 MVOCs and AH was associated with a significant increase in the case status and asthma risks in an additive scale.