main line • n. a chief railroad line: [as adj.] a main-line station. ∎ a principal route, course, or connection: the main line of evolution. ∎ a chief road or street. ∎ inf. a principal vein as a site for a drug injection.• v. (main·line) [tr.] inf. inject (a drug) intravenously: Mariella mainlines cocaine five to seven times a day. DERIVATIVES: main·lin·er n.