The effects of the cannabinoids, Δ9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD), on the primary-like immune response were investigated in primary cultures of mouse splenocytes. Splenocyte cultures were stimulated with sheep erythrocytes in vitro and incubated with cannabinoids for the first 24 h after antigenic stimulation (prior to initiation of DNA synthesis), from 24 h to 6 days after antigenic stimulation, and for the entire 5-day period. THC (1 and 5 μM) and CBD (5 μM) depressed the primary-like immune response of stimulated mouse splenocytes when incubated for the first 24 h after antigenic stimulation and the entire 6-day culture period. CBN did not show any measurable suppression of the primary-like immune response. Treatment of splenocyte cultures with cannabinoids after the first 24 h after antigenic stimulation showed no impairment of the in vitro primary-like immune respon