Griffith used two strains of Streptococcus pneumoniae. These bacteria infect mice, Griffith's favorite animals. He used a type III-S (smooth) and type II-R (rough) strain. The III-S strain covers itself with a polysaccharide capsule that protects it from the host's immune system. This means that the host will die. The II-R strain does not have that protective shield around it and is killed by the host's immune system.
In this experiment, bacteria from the III-S strain were killed by heat, and their remains were added to II-R strain bacteria. While neither harmed the mice on their own, the blend of the two was able to kill mice.
Griffith was also able to get both live II-R and live III-S strains of S. pneumoniae from the blood of these dead mice. He concluded that the type II-R had been "transformed" into the lethal III-S strain by a "transforming principle" that was somehow part of the dead III-S strain bacteria.
Today, we know that the "transforming principle" Griffith saw was the DNA of the III-S strain bacteria. While the bacteria had been killed, the DNA had survived the heating process and was taken up by the II-R strain bacteria. The III-S strain DNA contains the genes that form the shielding polysaccharide part from attack. Armed with this gene, the former II-R strain bacteria were now protected from the host's immune system and could kill the host.
- Lorenz MG, Wackernagel W (1994). "Bacterial gene transfer by natural genetic transformation in the environment". Microbiol. Rev. 58 (3): 563–602. PMID 7968924. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=7968924.
- Downie AW (1972). "Pneumococcal transformation--a backward view. Fourth Griffith Memorial Lecture". J. Gen. Microbiol. 73 (1): 1–11. PMID 4143929.
- Lederberg, Joshua 1994. The transformation of genetics by DNA: an anniversary celebration of Avery, Macleod and McCarty (1944). In James F. Crow and William F. Dove (eds) Anecdotal, historical and critical commentaries on genetics. Genetics Society of America. 
- Hartl, Daniel and Jones, Elizabeth 2005. Genetics: analysis of genes and genomes. 6th ed, Jones & Bartlett. Template:Catalog lookup linkScript error: No such module "check isxn".
- The original experiment by Griffith. Original article and 35th anniversary reprint available.
- Avery, MacLeod, and McCarty (1944). "Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a Desoxyribonucleic Acid fraction isolated from Pneumococcus Type III". Journal of Experimental Medicine 79 (1): 137–58. doi:10.1084/jem.79.2.137.