I know the USA only made it to Italia '90 by the skin of their teeth, but South Africa missed 2006 completely. Has it ever happened before? (well, I know Uruguay didn't qualify for the 1926 World Cup, but there's a good reason for that) Always assuming South Africa actually get to host 2010, of course.
1998 FIFA World Cup host, FRANCE failed to qualfy for the 1994 FIFA World Cup which was held in the UNITED STATES. the French who only needed just a point in the last two qualifying matches, lost 2-1 to both ISRAEL & BULGARIA, allowing BULGARIA to qualify instead with a last minute goal.
the other host nations which has failed to qualify for the previous FIFA World Cup are SWEDEN in 1954 (host nation in 1958), CHILE in 1958 (host nation in 1962), MEXICO in 1982 (host nation in 1986) & of course, SOUTH AFRICA in 2006 (host nation in 2010)
ITALY (host nation in 1934) did not take part in the first ever FIFA World Cup in 1930 coz there was no qualifying matches at that time. the first ever FIFA World Cup tournament in URUGUAY in 1930 was open to all national teams affiliated with FIFA & many European teams declined to take part due to the duration and cost of travel. only 4 European teams (BELGIUM, YUGOSLAVIA, ROMANIA & FRANCE) agree to take part.