BACKGROUND: A glycerol throat spray containing cold-adapted cod trypsin (GCTS) deactivates common cold virus in vitro and decreases pharyngeal rhinovirus load after inoculation in humans. We relied on early self-diagnosis and evaluated two different scales to detect a treatment effect in naturally occurring common colds. METHODS: Adults were enrolled in this randomised, prospective, parallel group, single-blind study to begin treatment six times daily at first sign of a common cold or were assigned to a non-treated group. Jackson\'s symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 quality of life (QoL) domain were recorded daily by subjects and area under the curve over 12 days (AUC1-12) calculated. RESULTS: Treatment resulted in reduced symptoms with an AUC1-12 of 45.1 +/- 32.5 for Jackson scores compared to 53.8 +/- 35.7 in the controls (p = 0.023). AUC1-12 for the 9-item WURSS-21 QoL domain was likewise improved, 113.6 +/- 107.7 and 152.7 +/- 126.3 (p = 0.006), respectively. During the first four days fewer of the treated subjects (35.3%) used rescue medication than did the control group (50.4%, p = 0.014). CONCLUSIONS: Reduction in common cold symptoms was seen with treatment with a glycerol throat spray containing cold-adapted cod trypsin. This effect was best detected with the 9-item WURSS-21 QoL domain.