This article traces the development of the design of experiments from origins in the mind and professional experience of R.A. Fisher between 1922 and 1926. The article indicates how the analysis of variance procedure stimulated design, being justified by the principle of randomization that Fisher introduced with the analysis, and exploited by his use of blocking and replication. The article indicates the radically new form and efficiency of factorial block designs, shows the further advantages accruing to factorial arrangements through confounding, and suggests how Fisher's close collaboration with experimenters stimulated these developments.