We compared the efficacy of penicillin V and amoxycillin treatment with placebo in 70 adult patients from Norwegian family practice with a clinical diagnosis of acute sinusitis and mucosal thickening on CT, but without fluid level or total opacification. The study was randomized and double-blind. Three different outcomes were evaluated; subjective status after 10 days of treatment, difference in clinical score between day 0 and day 10, and duration of the illness episode. Amoxycillin and penicillin V gave no better response to treatment than placebo, evaluated by all three outcome measures. The median duration of the sinusitis episode was 10 days in the amoxycillin- and placebo groups and 13 days in the penicillin-V group. In patients with a clinical diagnosis of acute sinusitis, fluid level and total opacification on CT are good criteria to differentiate between groups of patients that need or do not need antibiotic treatment.